1. Field of the Invention
The invention relates to a universal method and apparatus for determining, in real time, the individual concentrations of fluid constituents of any mixture of a predetermined number of fluids using, in the preferred embodiment, fluidic sensors. Further, the invention relates to a method and apparatus for determining or verifying the identity and/or purity of a single gas or an unknown gas in a mixture of gasses.
2. Description of the Prior Art
The determination of the relative concentrations of gasses in a mixture has been the subject of numerous inventions and intensive research over the years. Particularly, when noxious, poisonous or otherwise hazardous gasses are present, knowledge of the amount of such gasses is important to alert personnel in the area of any potential danger. In medical and clinical settings, awareness of the concentrations of respired gasses is important in the determination of patient metabolic conditions, especially the relative and absolute amounts of oxygen and carbon dioxide which provide information on the metabolization of oxygen as well as respiratory functioning. Under operating room conditions, anesthesiologists must be careful in administering anesthesia gasses and do so as a function of metabolic rate, and also must be aware of the absolute amount of anesthetic being provided in order to prevent overdosing or underdosing which would cause a patient to be aware during an operation. Also, when several different potent anesthetics must be administered during a procedure, the net amounts of the anesthetics need to be monitored to prevent overdosing.
Multiple medical gas monitors (MMGMs) continuously sample and measure inspired and exhaled (end-tidal) concentrations of respiratory gasses, including anesthetic gasses during and immediately following administration of anesthesia. These monitors are required since an overdose of anesthetic agent, and/or too little oxygen, can lead to brain damage and death, whereas too little agent results in insufficient anesthesia and subsequent awareness. The current development of these monitoring devices is described in the extensive anesthesia and biomedical engineering literature. Complete and specific information about the principles and applications of these devices is well reviewed in several recent texts (see, e.g., Lake, Clinical Monitoring, W B Saunders Co., pp. 479-498 (ch. 8),1990, incorporated herein by reference in its entirety), manufacturer's and trade publications (see, e.g., ECRI, "Multiple Medical Gas Monitors, Respired/Anesthetic", August 1983, incorporated herein by reference in its entirety), and in extensive anesthesia literature describing this equipment and its principles, methods and techniques of operation.
Medical gas monitoring provides the clinician with information about the patients physiologic status, verifies that the appropriate concentrations of delivered gases are administered, and warns of equipment failure or abnormalities in the gas delivery system. These monitors display inspired and exhaled gas concentrations and may sound alarms to alert clinical personnel when the concentration of oxygen (O.sub.2), carbon dioxide (CO.sub.2), nitrous oxide (N.sub.2 O), or anesthetic agent falls outside the desired set limits.
Most MMGMs utilize side-stream monitoring wherein gas samples are aspirated from the breathing circuit through long, narrow-diameter tubing lines. A water trap, desiccant and/or filter may be used to remove water vapor and condensation from the sample before the gas sample reaches the analysis chamber. Gas samples are aspirated into the monitor at either an adjustable or a fixed flow rate, typically from 50 to 250 ml/min. Lower rates minimize the amount of gas removed from the breathing circuit and, therefore, from the patient's tidal volume; however, lower sampling flow rates increase the response time and typically reduce the accuracy of conventional measurements. These gas monitors eliminate the exhaust gas through a scavenging system or return certain gas constituents to the patients breathing circuit.
There are several methods and techniques of anesthetic gas monitoring that are currently used. These methods and techniques are briefly reviewed below to distill their intrinsic advantages and disadvantages. A brief comparison is provided that includes both stand-alone and multi-operating room gas monitors that can determine concentrations of anesthetic and respiratory gases in the patient breathing circuit during anesthesia. Much of the research and development of these monitors have followed the long use of similar detector principles from analytical chemistry.
Because of the chemically diverse substances that they measure, MMGMs commonly combine more than one analytical method. Most MMGMs measure concentrations of halogenated anesthetic agents, CO.sub.2, and N.sub.2 O using nondispersive infrared (IR) absorption technology; however, there are others that use photoacoustic spectroscopy, based on the sound produced when an enclosed gas is exposed to pulsed optical energy. Other MMGMs use a piezoelectric method to measure anesthetic agent concentration. Electrochemical (e.g., galvanic)fuel cells and/or paramagnetic sensors are typically used to measure oxygen concentration, primarily because of their performance characteristics. Some MMGMs also have built-in or modular pulse oximeters to monitor tissue oxygen perfusion, although there is a major problem with the ambiguity between the presence of oxygen and carbon monoxide because hemoglobin bonds with both oxygen and carbon monoxide and conventional single wavelength pulse oximeters cannot distinguish between the two.
Infrared analyzers have been used for many years to identify and assay compounds for research applications. More recently, they have been adapted for respiratory monitoring of CO.sub.2, N.sub.2 O and halogenated agents. Dual-chamber nondispersive IR spectrometers pass IR energy from an incandescent filament through the sample chamber and an identical geometry but air-filled reference chamber. Each gas absorbs light at several wavelengths, but only a single absorption wavelength is selected for each gas to determine the gas concentration. The light is filtered after it passes through the chambers, and only that wavelength selected for each gas is transmitted to a detector. The light absorption in the analysis chamber is proportional to the partial pressure (e.g., concentration) of the gas. To detect halothane, enflurane, isoflurane, and other related potent anesthetics, most manufacturers use a wavelength range around 3.3 .mu.m, the peak wavelength at which the hydrogen-carbon bond absorbs light. In one monitor that identifies and quantifies halogenated agents, the analyzer is a single-channel, four-wavelength IR filter photometer. In this monitor, each of four filters (i.e., one for each anesthetic agent and one to provide a baseline for comparison) transmits a specific wavelength of IR energy, and each gas absorbs differently in the selected wavelength bands. In another monitor, the potent anesthetic agent is assayed by determining its absorption at three different wavelengths of light. The (Vickers Medical) Datex Capnomac, a multi-gas anesthetic agent analyzer, is based on the absorption of infrared radiation. This unit accurately analyzes breath-to-breath changes in concentrations of CO.sub.2, NO.sub.2, and N.sub.2 O and anesthetic vapors (See, McPeak et al., "Evaluation of a multigas anaesthetic monitor: the Datex Capnomac", Anaesthesia, Vol. 43, pp.1035-1041, 1988, incorporated herein by reference in its entirety). It is accurate with CO.sub.2 for up to 60 breaths/min, and 30 breaths/min for O.sub.2, but N.sub.2 O and anesthetic vapors show a decrease in accuracy at frequencies higher than 20 breaths/min. The use of narrow wave-band filters to increase specificity for CO.sub.2 and N.sub.2 O makes the identification of the anesthetic vapors which are measured in the same wave band more difficult. The Inov3100 near-infrared spectroscopy monitor has been offered as a monitor for intracerebral oxygenation during anesthesia and surgery. Studies done on this monitor indicate that it needs a wide optode separation and the measurements are more likely those of the external carotid flow rather than the divided internal carotid circulation (see Harris et al., "Near infrared spectroscopy in adults", Anaesthesia Vol. 48, pp. 694-696, 1993, incorporated herein by reference in its entirety). Almost all non-dispersive infrared (NDIR) devices suffer from cross-sensitivities that may be present, thereby requiring extensive calibration and correction when mixture of gasses flow. The presence of O.sub.2, in particular, presents a major problem.
Photoacoustic spectroscopy measures the energy produced when a gas is expanded by absorption of optical radiation; the energy is pulsed by rotating a disk with three concentric slotted sections between the optical source and the measurement chamber. The acoustic pressure fluctuations created occur with a frequency between 20 and 20,000 Hz, producing sound that is detected with a microphone and converted to an electrical signal. Each gas (e.g., anesthetic agent, CO.sub.2, N.sub.2 O) exhibits a pronounced photoacoustic effect at a different wavelength of incident light energy. This method, however, cannot distinguish which halogenated agent is present. A similar microphone can to used to detect the pulsating pressure changes in a paramagnetic oxygen sensor (e.g., magnetoacoustics). The microphone detects the pulsating pressures from all four gases simultaneously and produces a four component signal. A monitor using IR photoacoustic technology has been developed that can quantify all commonly respired/anesthetic gasses except N.sub.2 and water vapor (the presence of which adversely affects accuracy). The Bruel & Kjaer Multigas Monitor 1304 uses photoacoustic spectroscopy and also incorporates a pulse oximeter. It has some advantages over the Data Capnomac since it uses the same microphone for detection of all gases, displaying gas concentration with a real-time relationship. There has been found to be a considerable decrease in accuracy when a hybrid sampling tube was used rather than a nafion tube, indicating the need for the additional expense of using a nafion sampling tube to ensure the elimination of water vapor (see McPeak et al., "An Evaluation of the Bruel and Kjaer monitor 1304", Anaesthesia, Vol. 47, pp. 41-47, 1992, incorporated herein by reference in its entirety).
The piezoelectric method is also used to measure the concentration of a selected halogenated agent. The sample is pumped through a chamber containing two crystals: a reference crystal and a second crystal that has been coated with an organophillic compound to adsorb the anesthetic gas. The resulting increase in mass changes the coated crystal's resonant frequency in direct proportion to the concentration of anesthetic gas in the sample, thereby generating a voltage that is displayed as a percentage of vapor. One piezoelectric-based unit has a separate nondispersive IR sensor that differentiates inhalation and exhalation to detect breaths, as well as an integral galvanic fuel cell that measures oxygen concentration before the sampled gas is returned to the breathing circuit. These devices also demonstrate cross-sensitivity to other gasses that may be present.
Mass and Raman spectrometers can measure and identify all respiratory and anesthetic gasses including N.sub.2 and in some cases helium. The application of mass spectrometry to the field of monitoring anesthetic gases allows real-time measurement of all inspired and exhaled gasses. Unfortunately, the cost and complexity of this instrumentation has necessitated its being used in a time-sharing fashion among multiple operating rooms. Raman scattering was first heralded as an improvement to mass spectrometry (see Westenskow et al., "Clinical evaluation of a Raman scattering multiple gas analyzer", Anesthesiology, Vol. 70, pp. 350-355, 1989, incorporated herein by reference in its entirety), although there have been some reservations about this technique (see Severinghaus et al, "Multi-operating room monitoring with one mass spectrometer", Acta Anaesthesiol Scan [Suppl] 70:186-187, 1987, incorporated herein by reference in its entirety). The (Ohmeda) Rascal II multigas analyzer, with pulse oximeter, uses a Raman scattering of laser light to identify and quantify O.sub.2, N.sub.2, CO.sub.2, N.sub.2 O and anesthetic agents. It is stable and can monitor the gasses including N.sub.2 and CO.sub.2 accurately for a wide range of concentrations. However, there is a possibility of some destruction of volatile agent during the analysis since the concentration of Halothane does appear to fall when recirculated and there is a gain of the volatile agent of as much as fifteen percent. There is some concern over the reliability of the hardware, software and laser light source (see Lockwood et al., "The Ohmeda Rascall II", Anaesthesia, Vol. 49, pp. 44-53, 1994, incorporated herein by reference in its entirety) which is currently being addressed by others, which necessitates frequent and costly calibration and adjustment.
Other related medical gas monitoring approaches include specific techniques for monitoring oxygen concentration. As described in the above-referenced text by Lake, a commonly used oxygen analyzer detector is based on a polarographic method. In yet another analyzer which uses a galvanic cell, oxygen diffuses through a semipermeable membrane, reaches a reducing electrode, and is carried as a reaction product to another (e.g., reference) electrode, where it frees electrons. The rate at which oxygen diffuses into the cell and generates voltage is directly proportional to the partial pressure of oxygen diffusing through the membrane. Several factors affect the output and lifetime of the cells. During its life, the electrode loses water, some water diffuses out as oxygen which enters the cell while some water is consumed through oxidation, and eventually requires replacement.
Paramagnetic sensors are typically used specifically for measuring oxygen concentration. The design of this sensor is based on oxygen's high degree of sensitivity (e.g., compared to other gasses) to magnetic forces. The sensor includes a symmetrical, two chambered cell with identical chambers for the sample and reference gas (e.g., air). These cells are joined at an interface by a differential pressure transducer or microphone. Sample and reference gases are pumped through these chambers in which a strong magnetic field surrounding the region acts on the oxygen molecules to generate a pressure difference between the two sides of the cell, thereby causing the transducer to produce a voltage proportional to the oxygen concentration. This device, as is the case with most devices, requires frequent calibration, is costly in and of itself, and depends on certain operator skills for proper operation.
Table 1, derived from Eisenkraft et al., "Monitoring Gases in the Anesthesia Delivery System", Anesthesia Equipment: Principles and Applications, Mosby-Year Book, pp.201-220, 1993, incorporated herein by reference in its entirety, provides a summary of methods and techniques to monitor respiratory gasses.
TABLE 1 METHOD O.sub.2 CO.sub.2 N.sub.2 O Anes N.sub.2 He Ar Mass Spectroscopy YES YES YES YES YES YES YES Raman Spectroscopy YES YES YES YES YES YES YES IR - Light NO YES YES YES NO NO NO Spectroscopy IR - Photo Acoustics NO YES YES YES NO NO NO Piezoelectric NO NO NO YES NO NO NO Resonance Polarography YES NO NO NO NO NO NO Fuel Cell YES NO NO NO NO NO NO Paramagnetic Analysis YES NO NO NO NO NO NO Magnetoacoustics YES NO NO NO NO NO NO
A review of the background and significance of MMGM would be incomplete without an expression of the impact that patient safety has had on the impetus for recent gains in technology and the need for additional improvements. Clearly, the intrinsic dangers in the conduct of anesthesia have been long understood. However, it has not been until the Department of Anesthesia at the Harvard Teaching Hospital decided to create a set of basic monitoring standards that non-invasive respiratory gas monitoring became widely available and its use common place. The Harvard Medical School Standard for Anesthesia requires:
1) the ability to assure safety and effectiveness of the application of anesthetic agents; PA1 2) simplicity of methods and techniques which translate directly into reliability, low acquisition cost, low cost to service, operate and maintain; PA1 3) appropriate accuracy, precision and stability to monitor relative concentrations of necessary anesthetic gases particularly CO.sub.2, O.sub.2, and the potent anesthetic gas agents; and PA1 4) appropriate time response and acceptable delays in monitoring changes in relative concentrations of gasses with respect to respiration rates during anesthesia.
Medical malpractice liability insurance companies have lowered their risk liabilities and premiums to anesthesiologists who guarantee to use pulse oximetry and end-tidal CO.sub.2 tension monitoring whenever possible (see Swedlow, "Respiratory Gas Monitoring", Monitoring in Anesthesia, pp. 27-50, Boston, Butterworth-Heinemann, 3rd edition, 1993, incorporated herein by reference in its entirety). The argument for providing additional patient safety continues to be a powerful incentive to improve and enhance the methods and techniques to provide increased knowledge of the monitoring of anesthetic gasses.
Safety considerations require that the presence of nitrogen be detected as this provides warning of air embolisms, as well as alerting to possible loss of integrity of the breathing circuit, as air (with N.sub.2) is introduced. A major disadvantage of most conventional gas monitors is that they do not measure N.sub.2. A major disadvantage of present-day MMGMs which use one or a combination of the above-cited techniques is their high cost. A further disadvantage is that many of these sensors can determine the concentrations of only certain types of gasses or a limited number of gasses.
Fluidic gas concentration sensors offer a low-cost alternative to the devices that use the above techniques. However, known fluidic gas concentration sensors, either oscillators or orifice-capillary pairs, have been capable of detecting concentrations of gasses in a mixture of at most two gasses, and, until only recently, the pressures could not be measured with sufficient accuracy at low cost, to make systems practical.
More particularly, prior fluidic gas concentration sensors, either oscillators (for example, that disclosed in U.S. Pat. No. 3,765,224 to Villarroel et al., the disclosure of which is incorporated herein by reference in its entirety) whose frequency is a function of the speed of sound, and hence, the ratio of specific heats of a gas mixture, or orifice-capillary pairs (for example, that disclosed in U.S. Pat. No. 3,771,348 to Villarroel, the disclosure of which is incorporated herein by reference in its entirety) where the pressure at the junction between the two is a function of density and viscosity of the mixture, were based on measuring the relative concentrations of two gasses in a mixture. Multiple gas analysis may subsequently be accomplished only by physically or chemically separating multiple gas mixtures into multiple two-gas mixtures which may then be separately analyzed. Multiple scrubber approaches, however, cannot be implemented in real time because of the very long delay times associated with passing the gas samples through the volume of a scrubber at the relatively low flow rates associated with the sample streams. Thus, despite the affordability of fluidic sensors, they have not been widely used in MMGMs to measure concentrations of medical gasses during the administration of anesthesia.
Another application for gas analysis in the medical field is the determination or verification of the identity and purity of a gas flowing from a source. Gasses such as oxygen, nitrous oxide, and volatile anesthesia gasses are supplied from sources to patients in operating rooms, intensive care units and hospital rooms. For example, oxygen is often supplied through a wall outlet which is fed from a remotely located oxygen tank. Anesthesia is typically stored in a vaporizer and dispensed by imposing a carrier gas (e.g., O.sub.2) through a flow meter which is used to control the amount of anesthesia vapor being supplied. An anesthesia machine may contain several volatile anesthetic agents, each in a separate container with a separate flow meter. While precautions are generally taken to ensure that the correct type of gas is flowing from a source, it is possible for an incorrect gas or a contaminated gas to be supplied. For example, it may be possible for a nitrous oxide tank to be erroneously connected to an oxygen supply line or for one type of anesthesia to be erroneously stored in an anesthesia container labeled as another type of anesthesia. Further, the purity of a gas may be compromised between the source and the point of delivery. For example, an oxygen supply line could be damaged or ruptured, thereby allowing atmospheric gasses to enter the supply line and to be delivered along with a reduced concentration of oxygen.
Use of known gas analyzers to verify the identity and purity of gasses at a source or at a point of delivery would be expensive and impractical in many circumstances. For example, it would be prohibitively expensive to integrate a conventional gas analyzer into every oxygen supply outlet in a hospital. Likewise, it would be expensive to incorporate a conventional gas analyzer into each container of anesthesia gas in a hospital. Further, conventional gas analyzers require periodic calibration which would make such gas analyzers impractical in large numbers. Thus, a low maintenance, lost cost gas analyzer is needed to verify the identity and purity of gasses at a source or point of delivery.